Current therapies to treat opportunistic infections associated with the Acquired Immunodeficiency Syndrome (AIDS) are either highly toxic, extremely expensive or marginally effective. Since these infections produce significant morbidity and mortality in patients with AIDS, the National Institute of Allergy and Infectious Diseases facilitates discovery and development of novel therapies for the treatment of AIDS-related opportunistic infections. This includes providing contract resources for identifying and developing potential new drugs, and conducting efficacy evaluations in animal models, a critical component in the drug approval process. At present there is no recommended therapy for infection with Cryptosporidium parvum, in part, because of the lack of in vitro culture systems and small animal models that are suitable for drug evaluations. Phase I of this project will support three agencies in the development of in vitro and in vivo test systems. Thereafter in Phase 2 of the program, one or more of these agencies will be selected to apply their systems toward evaluating the efficacy of potential new drugs against Cryptosporidium. The culture systems and animal models developed through these contracts will ultimately provide NIAID with the necessary resources to provide critical support for investigator-initiated drug discovery, to stimulate private sector sponsorship of compounds with demonstrated efficacy, and to select the best drug candidates for clinical trials. Phase I of the contract indicated above will adapt the SCID mouse for primary screening of candidate therapies against Cryptosporidium infection, and the CD/SPF piglet model for further evaluating drug candidates that are active in mice. Parameters for drug evaluations will include improvement of clinical symptoms, reduced parasite shedding, and reduced parasite load and tissue pathology. If selected for Phase 2 of the program, the contractor will systematically apply an animal model toward drug evaluations as well as develop in vitro systems suitable for primary screening of drugs against cultured parasites.